EPIGENOMICS, RNA, AND GENE REGULATION RESEARCH PROGRAM (ERGR) ABSTRACT The Epigenomics, RNA, and Gene Regulation Research Program (ERGR), led by Michael Carey, PhD (Program Director) and Siavash Kurdistani, MD (Program Co-Director), is the most basic of the JCCC Research Programs. Program objectives are to support exceptional JCCC researchers and teams, to ensure ongoing Program robustness with strategic recruitments and training, and to innovate breakthroughs in gene regulation, RNA biology, and bioinformatics with impact in cancer. The expectation is that ERGR investigator discoveries will uncover vulnerabilities for targeting by novel diagnostic and anti-tumor treatment strategies. ERGR investigators employ a range of model systems, from yeast and plants to cancer cells and small animals, to elucidate mechanisms of gene regulation, from chromatin and transcription to RNA biology, to understand and dissect alterations in cancer. Program studies extend to physiological and pathological processes implicated in cancer including cell differentiation, inflammation, and lipid metabolism. ERGR leads in developing new technologies and methodologies, such as advanced informatics for high-throughput experimental tools, and provides expertise to researchers in all six JCCC Research Programs. Although focused on epigenomics and gene regulatory mechanisms, ERGR strives to translate new knowledge to preclinical and clinical settings, with Program discoveries underpinning clinical HDAC inhibitor development and cell free DNA diagnostics. The ERGR Research Program has 33 members drawn from five UCLA schools and partner institution, Caltech, representing 13 departments. As of March 1, 2019, Program support was $11,256,579 in direct cost funding, of which $9,904,290 (88%) is peer-reviewed, and $1,031,199 (9%) is NCI funding. Program discoveries resulted in 506 publications during the prior project period, of which 10% were intra-programmatic collaborations, and 19% were inter-programmatic collaborations. In addition, 271 (54%) Program publications were with external collaborators and 337 (67%) of publications were in high-impact (IF ?10, or field leading) journals. As an example, one achievement in the prior period was enormous strengthening of bioinformatics via recruitment. Scientifically, studies revealed how a viral oncogene exploits cell machinery to induce cell cycling and simultaneously block an anti-viral immune response. Additionally, new insights into the metabolic dependencies of stem cell self- renewal and differentiation informed how such dependencies may provide a permissive environment for tumorigenesis in the presence of pre-disposing genetic mutations. ERGR investigators cultivate a collegial environment with many structured opportunities to exchange ideas, research findings, and scientific discussions amongst Program faculty, postdocs, and students. These interactions help establish valuable collaborations that raise the quality of Program science and inspire interest in cancer-related problems. An ERGR Program guiding principle is to foster the discovery of fundamental biological processes whose alterations may contribute to cancer development and progression, which supports the ultimate JCCC goal of defeating this dreaded disease.